A Tighter Relaxation for the Relative Pose Problem Between Cameras

This paper tackles the resolution of the Relative Pose problem with optimality guarantees by stating it as an optimization problem over the set of essential matrices that minimizes the squared epipolar error. We relax this non-convex problem with its Shor’s relaxation, a convex program that can be solved by off-the-shelf tools. We follow the empirical observation that redundant but independent constraints tighten the relaxation. For that, we leverage equivalent definitions of the set of essential matrices based on the translation vectors between the cameras. Overconstrained characterizations of the set of essential matrices are derived by the combination of these definitions. Through extensive experiments on synthetic and real data, our proposal is empirically proved to remain tight and to require only 7 milliseconds to be solved even for the overconstrained formulations, finding the optimal solution under a wide variety of configurations, including highly noisy data and outliers. The solver cannot certify the solution only in very extreme cases, e.g.noise 100 pix and number of pair-wise correspondences under 15. The proposal is thus faster than other overconstrained formulations while being faster than the minimal ones, making it suitable for real-world applications that require optimality certification.Open Access funded by Universidad de Malaga / CBUA

Sostenibilidad de recursos energéticos fosiles y minerales: Uso racional de abastecmiento y cosumo

Esta primera parte referente a la “Garantía del Suministro Energético” sirve como introducción al informe realizado por este Grupo de Trabajo sobre “Sostenibilidad de los Recursos Energéticos Fósiles y Minerales: Uso Racional en el Abastecimiento y Consumo”. Queremos, en primer lugar, agradecer al Congreso del Medio Ambiente la oportunidad de poder debatir este tema de trascendencia capital para la economía global y, de forma especial, a José Sierra, Consejero de la Comisión Nacional de Energía su contribución desinteresada e imprescindible para el desarrollo de este trabajo

The mutational landscape of human olfactory G protein-coupled receptors

Olfactory receptors (ORs) constitute a large family of sensory proteins that enable us to recognize a wide range of chemical volatiles in the environment. By contrast to the extensive information about human olfactory thresholds for thousands of odorants, studies of the genetic influence on olfaction are limited to a few examples. To annotate on a broad scale the impact of mutations at the structural level, here we analyzed a compendium of 119,069 natural variants in human ORs collected from the public domain. OR mutations were categorized depending on their genomic and protein contexts, as well as their frequency of occurrence in several human populations. Functional interpretation of the natural changes was estimated from the increasing knowledge of the structure and function of the G protein-coupled receptor (GPCR) family, to which ORs belong. Our analysis reveals an extraordinary diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a significant number of changes occurring at the structurally conserved regions. A particular attention is paid to mutations in positions linked to the conserved GPCR activation mechanism that could imply phenotypic variation in the olfactory perception. An interactive web application (hORMdb, Human Olfactory Receptor Mutation Database) was developed for the management and visualization of this mutational dataset. We performed topological annotations and population analysis of natural variants of human olfactory receptors and provide an interactive application to explore human OR mutation data. We envisage that the utility of this information will increase as the amount of available pharmacological data for these receptors grow. This effort, together with ongoing research in the study of genetic changes in other sensory receptors could shape an emerging sensegenomics field of knowledge, which should be considered by food and cosmetic consumer product manufacturers for the benefit of the general population. https://doi.org/10.13039/5011000110335https://doi.org/10.13039/5011000110333https://doi.org/10.13039/5011000110336https://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033_https://doi.org/10.13039/501100011033_https://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033$https://doi.org/10.13039/501100011033ahttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033Ahttps://doi.org/10.13039/501100011033ghttps://doi.org/10.13039/501100011033ehttps://doi.org/10.13039/501100011033nhttps://doi.org/10.13039/501100011033chttps://doi.org/10.13039/501100011033ihttps://doi.org/10.13039/501100011033ahttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033Ehttps://doi.org/10.13039/501100011033shttps://doi.org/10.13039/501100011033thttps://doi.org/10.13039/501100011033ahttps://doi.org/10.13039/501100011033thttps://doi.org/10.13039/501100011033ahttps://doi.org/10.13039/501100011033lhttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033dhttps://doi.org/10.13039/501100011033ehttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033Ihttps://doi.org/10.13039/501100011033nhttps://doi.org/10.13039/501100011033vhttps://doi.org/10.13039/501100011033ehttps://doi.org/10.13039/501100011033shttps://doi.org/10.13039/501100011033thttps://doi.org/10.13039/501100011033ihttps://doi.org/10.13039/501100011033ghttps://doi.org/10.13039/501100011033ahttps://doi.org/10.13039/501100011033chttps://doi.org/10.13039/501100011033ihttps://doi.org/10.13039/501100011033óhttps://doi.org/10.13039/501100011033nhttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033$https://doi.org/10.13039/501100011033dhttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033$https://doi.org/10.13039/501100011033fhttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033Phttps://doi.org/10.13039/501100011033Ihttps://doi.org/10.13039/501100011033Dhttps://doi.org/10.13039/5011000110332https://doi.org/10.13039/5011000110330https://doi.org/10.13039/5011000110331https://doi.org/10.13039/5011000110339https://doi.org/10.13039/501100011033-https://doi.org/10.13039/5011000110331https://doi.org/10.13039/5011000110330https://doi.org/10.13039/5011000110339https://doi.org/10.13039/5011000110332https://doi.org/10.13039/5011000110334https://doi.org/10.13039/5011000110330https://doi.org/10.13039/501100011033Rhttps://doi.org/10.13039/501100011033Bhttps://doi.org/10.13039/501100011033-https://doi.org/10.13039/501100011033Ihttps://doi.org/10.13039/5011000110330https://doi.org/10.13039/5011000110330https://doi.org/10.13039/50110001103

Lymphocyte Profile and Immune Checkpoint Expression in Drug-Induced Liver Injury: An Immunophenotyping Study

The identification of specific HLA risk alleles in drug-induced liver injury (DILI) points toward an important role of the adaptive immune system in DILI development. In this study, we aimed to corroborate the role of an adaptive immune response in DILI through immunophenotyping of leukocyte populations and immune checkpoint expressions. Blood samples were collected from adjudicated DILI (n = 12), acute viral hepatitis (VH; n = 13), acute autoimmune hepatitis (AIH; n = 9), and acute liver injury of unknown etiology (n = 15) at day 1 (recognition), day 7, and day >30. Blood samples from patients with nonalcoholic fatty liver disease (NAFLD; n = 20) and healthy liver controls (HLCs; n = 54) were extracted at one time point. Leukocyte populations and immune checkpoint expressions were determined based on cell surface receptors, except for CTLA-4 that was determined intracellularly, using flow cytometry. At recognition, DILI demonstrated significantly higher levels of activated helper T-cell (P < 0.0001), activated cytotoxic T-cells (P = 0.0003), Th1 (P = 0.0358), intracellular CTLA-4 level in helper T-cells (P = 0.0192), and PD-L1 presenting monocytes (P = 0.0452) than HLC. These levels approached those of HLC over time. No significant differences were found between DILI and VH. However, DILI presented higher level of activated helper T-cells and CTLA-4 than NAFLD and lower PD-L1 level than AIH. Our findings suggest that an adaptive immune response is involved in DILI in which activated CD4+ and CD8+ play an important role. Increased expression of negative immune checkpoints is likely the effect of peripheral tolerance regulation.The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI19/00883, PI16/01748, P18-RT-3364-2020, and PT20/000127). CIBERehd and Plataforma ISCiii Ensayos Clínicos are funded by Instituto de Salud Carlos III. Funding for open access charge: Universidad de Málaga/CBUA. The funding sources had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report, or in the decision to submit the manuscript for publication

Incidence and prevalence of acute hepatitis E virus infection in patients with suspected Drug-Induced Liver Injury in the Spanish DILI Registry

Background and Aims: Drug-induced liver injury (DILI) presents with a wide phenotypic spectrum requiring an extensive differential diagnosis. Hepatitis E virus (HEV) is not systematically ruled out during acute hepatitis assessment in Spain. The aims of this study were to establish the role of HEV infection and its phenotypic presentation in patients initially suspected of DILI and to determine the anti-HEV seroprevalence rate. Methods: An analysis of 265 patients with suspected DILI and considered for enrolment in the Spanish DILI Registry and 108 controls with normal liver profiles was undertaken. Anti-HEV Immunoglobulin (Ig) G antibodies were analyzed in serum from all subjects. In those with serum samples extracted within 6 months from liver damage onset (n=144), HEV antigen (Ag) and anti- HEV IgM antibodies were tested in duplicate by ELISA. In addition, RT-PCR was performed externally in 8 patients. Results: Out of 144 patients, 12 (8%) were positive for anti-HEV IgM, mean age 61 years. Underlying hepatic diseases (OR=23.4, p20 folds upper limit of normal (OR=10.9, p=0.002) were associated with the diagnosis of acute hepatitis E. The overall anti-HEV IgG seroprevalence rate was 35%, evenly distributed between patients with suspected DILI (34%), and controls (39%). Conclusions: HEV seroprevalence and acute hepatitis E rates are relatively high in Spain. A search for active HEV infection is therefore advised in patients assessed for suspicion of DILI, particularly in patients with underlying liver diseases and high transaminase levels.The present study has been supported by grants of the Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional FEDER (contract numbers: FIS PI0274-2016, PI-0285- 2016, PI 18-01804, PI 18-00901, PT17/0017/0020, CM17/00243, JR16/00015, B-0002-2019, UMA-18-FEDERJA-193 and by the Agencia Española del Medicamento. SCReN and CIBERehd are funded by Instituto de Salud Carlos III. European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network, IMI2-Translational Safety Biomarker Pipeline (TransBioLine). The funding sources had no involvement in the study design, in the collection, analysis, and interpretation of data, in the writing of the report or in the decision to submit the manuscript for publicatio

Comparison of uniportal robotic-assisted thoracic surgery pulmonary anatomic resections with multiport robotic-assisted thoracic surgery: a multicenter study of the European experience

Background: Robotic-assisted thoracic surgery (RATS) has seen increasing interest in the last few years, with most procedures primarily being performed in the conventional multiport manner. Our team has developed a new approach that has the potential to convert surgeons from uniportal video-assisted thoracic surgery (VATS) or open surgery to robotic-assisted surgery, uniportal-RATS (U-RATS). We aimed to evaluate the outcomes of one single incision, uniportal robotic-assisted thoracic surgery (U-RATS) against standard multiport RATS (M-RATS) with regards to safety, feasibility, surgical technique, immediate oncological result, postoperative recovery, and 30-day follow-up morbidity and mortality. Methods: We performed a large retrospective multi-institutional review of our prospectively curated database, including 101 consecutive U-RATS procedures performed from September 2021 to October 2022, in the European centers that our main surgeon operates in. We compared these cases to 101 consecutive M-RATS cases done by our colleagues in Barcelona between 2019 to 2022. Results: Both patient groups were similar with respect to demographics, smoking status and tumor size, but were significantly younger in the U-RATS group [M-RATS =69 (range, 39-81) years; U-RATS =63 years (range, 19-82) years; P<0.0001]. Most patients in both operative groups underwent resection of a primary non-small cell lung cancer (NSCLC) [M-RATS 96/101 (95%); U-RATS =60/101 (59%); P<0.0001]. The main type of anatomic resection was lobectomy for the multiport group, and segmentectomy for the U-RATS group. In the M-RATS group, only one anatomical segmentectomy was performed, while the U-RATS group had twenty-four (24%) segmentectomies (P=0.0006). All M-RATS and U-RATS surgical specimens had negative resection margins (R0) and contained an equivalent median number of lymph nodes available for pathologic analysis [M-RATS =11 (range, 5-54); U-RATS =15 (range, 0-41); P=0.87]. Conversion rate to thoracotomy was zero in the U-RATS group and low in M-RATS [M-RATS =2/101 (2%); U-RATS =0/101; P=0.19]. Median operative time was also statistically different [M-RATS =150 (range, 60-300) minutes; U-RATS =136 (range, 30-308) minutes; P=0.0001]. Median length of stay was significantly lower in U-RATS group at four days [M-RATS =5 (range, 2-31) days; U-RATS =4 (range, 1-18) days; P<0.0001]. Rate of complications and 30-day mortality was low in both groups. Conclusions: U-RATS is feasible and safe for anatomic lung resections and comparable to the multiport conventional approach regarding surgical outcomes. Given the similarity of the technique to uniportal VATS, it presents the potential to convert minimally invasive thoracic surgeons to a robotic-assisted approach

Comparison of next-generation sequencing (NGS) and next-generation flow (NGF) for minimal residual disease (MRD) assessment in multiple myeloma

Detecting persistent minimal residual disease (MRD) allows the identification of patients with an increased risk of relapse and death. In this study, we have evaluated MRD 3 months after transplantation in 106 myeloma patients using a commercial next-generation sequencing (NGS) strategy (LymphoTrack®), and compared the results with next-generation flow (NGF, EuroFlow). The use of different marrow pulls and the need of concentrating samples for NGS biased the applicability for MRD evaluation and favored NGF. Despite that, correlation between NGS and NGF was high (R = 0.905). The 3-year progression-free survival (PFS) rates by NGS and NGF were longer for undetectable vs. positive patients (NGS: 88.7% vs. 56.6%; NGF: 91.4% vs. 50%; p < 0.001 for both comparisons), which resulted in a 3-year overall survival (OS) advantage (NGS: 96.2% vs. 77.3%; NGF: 96.6% vs. 74.9%, p < 0.01 for both comparisons). In the Cox regression model, NGS and NGF negativity had similar results but favoring the latter in PFS (HR: 0.20, 95% CI: 0.09-0.45, p < 0.001) and OS (HR: 0.21, 95% CI: 0.06-0.75, p = 0.02). All these results reinforce the role of MRD detection by different strategies in patient prognosis and highlight the use of MRD as an endpoint for multiple myeloma treatment

Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry

Background & aims: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. Methods: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. Results: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%).The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI19/00883, PI16/01748, PI18/00901, PI18/01804, PI-0285-2016, PI-0274-2016, PI-0310- 2018, PT17/0017/0020) and Agencia Española del Medicamento. CIBERehd and Plataforma ISCIII Ensayos Clinicos are funded by Instituto de Salud Carlos III. MRD holds a Joan Rodes (JR16/ 00015)/Acción B clinicos investigadores (B-0002-2019) and JSC a Rio Hortega (CM17/00243) research contract from ISCIII and Consejería de Salud de Andalucía. The funding sources had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report or in the de- cision to submit the manuscript for publication